Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment

Background: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retionic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. Methods: After treatment with 1 μg all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). Results: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. Conclusions: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves. © 1995 Wiley-Liss, Inc.     

User satisfaction with a real-time automated feedback system for general practitioners: a quantitative and qualitative study.

OBJECTIVE: The GRIF automated feedback system produces real-time comments on the appropriateness of diagnostic tests ordered by general practitioners (GPs) based on recommendations from accepted national and regional practice guidelines. We investigated the experiences of GPs with this system and, more specifically, with the recommendations produced by the system as well as their views on using this system in daily practice. SETTING: We tested the GRIF system in an experiment in a laboratory setting and in a daily practice trial. STUDY PARTICIPANTS: General practitioners. INTERVENTION: In the laboratory experiment, GPs used the GRIF system to assess the appropriateness of 30 request forms. Each of the GPs was confronted with requests they had submitted to the diagnostic unit of the hospital in the past. In the field trial, the GRIF system was applied during patient consultations for 1 year. MAIN OUTCOME MEASURES: We measured GPs' satisfaction with the system using a questionnaire, and also conducted group discussions (in the laboratory experiment) and in-depth interviews (in the field trial) to elicit GPs' opinions of and experiences with the system. In addition, we explored GPs' reasons for not accepting the comments offered by the GRIF system. RESULTS: The results show that the GPs in the laboratory experiment had more positive attitudes towards the system compared with participants in the field trial. All discussion groups and most of the GPs in the field trial regarded receiving the immediate feedback during the test ordering process as an important advantage. The most frequently mentioned reason to reject the recommendation was disagreement with the content and/or the recommendations in the practice guidelines. CONCLUSION: Apart from securing agreement on guideline content, a prerequisite for using GRIF in daily practice on a large scale is that more attention is paid to promotion of the guidelines and their adoption, and stimulation of a positive attitude towards the practice guidelines among the users.     

How the COVID-19 pandemic can distort risk adjustment of health plan payment

The European Journal of Health Economics - The COVID-19 pandemic has led to disruptions in healthcare utilization and spending. While some changes might persist (e.g. substitution of specialist...     

Transforming growth factor-beta plasma dynamics and post-irradiation lung injury in lung cancer patients.

PURPOSE: To investigate the relevance of transforming growth factor-beta (TGF-beta) dynamics in plasma for identification of patients at low risk for developing pneumonitis as a complication of thoracic radiotherapy (RT). PATIENTS AND METHODS: Non-small cell lung cancer patients undergoing conventional RT were included in the prospective study. Concentrations of TGF-beta were measured in the patients' plasma prior to and weekly during 6 weeks of RT. The incidence of symptoms of early post-irradiation lung injury, i.e. symptomatic radiation pneumonitis, was correlated with TGF-beta parameters. RESULTS: Forty-six patients were included in the study. Eleven patients (24%) developed symptomatic radiation pneumonitis. Absolute TGF-beta plasma levels did not differ between the groups of patients without or with pneumonitis. However, patients who developed pneumonitis tended to show increases in TGF-beta levels in the middle of the RT course relative to their pre-treatment levels while TGF-beta plasma levels of patients who did not develop pneumonitis tended to decrease over the RT treatment. The difference in the relative TGF-beta dynamics between the groups reached marginal significance in the third week of the treatment (P = 0.055) but weakened towards the end of the RT course. The utility of TGF-beta testing was evaluated at each RT week based on the test's ability to yield more accurate estimate of complication probability in an individual patient compared to empirically expected probability in similar group of patients. The ratio of TGF-beta level at week 3/week 0 being <1 showed an ability to improve the prediction of freedom from pneumonitis, yet with a large degree of uncertainty (wide confidence intervals). The accuracy of prediction deteriorated at later time points (weeks 4, 5 and 6) rendering the end-RT ratios without predictive power. CONCLUSIONS: We observed a trend of plasma TGF-beta concentration to decrease below the pre-treatment value during the RT treatment in patients who did not develop pulmonary complications after the RT treatment. However, this trend was not consistent enough to warrant safe decision-making in clinical setting.     

Evaluation of the use of reporter antigens in an auricular lymph node assay to assess the immunosensitizing potential of drugs.

Immune-mediated idiosyncratic drug reactions are a major problem for susceptible patients, physicians, and the pharmaceutical industry. Validated screening tools to assess the immunosensitizing capacity of orally or intravenously administered pharmaceuticals are currently not available. To date, the popliteal lymph node assay (PLNA) seems the most promising tool for this purpose. The PLNA has recently been extended with the use of reporter antigens (RA) that are coinjected together with the drug of interest. The measurement of isotypes of RA-specific antibody-secreting cells (ASC) enables the distinction of sensitizing chemicals and (nonsensitizing) irritants without radio-isotopic end points. However, the use of footpad injections raises ethical concerns. Therefore, we examined the use of RA after intradermal injection into the ear of BALB/c mice and measured RA-specific ASC in the draining auricular lymph node (ALN). We show that RA-specific IgG isotype ASC numbers are very useful and sensitive parameters to identify drug-induced hypersensitivity in both PLN and ALN. However, the type 1-associated parameters (CD8(+) cells, macrophages, IFN-gamma, TNF-alpha, and IL-1 beta) that are induced in the PLN by streptozotocin were less pronounced in the ALN. Thus, the PLNA may provide more immunologically relevant information on the mechanisms of certain chemical-induced hypersensitivity reactions. The RA-ALN assay may provide an alternative for the RA-PLNA; both assays can be used to distinguish sensitizing compounds from nonsensitizing ones.     

Presentation and interpretation of food intake data: Factors affecting comparability across studies

Non-uniform, unclear, or incomplete presentation of food intake data limits interpretation, usefulness, and comparisons across studies. In this contribution, we discuss factors affecting uniform reporting of food intake across studies. The amount of food eaten can be reported as mean portion size, number of servings or total amount of food consumed per day; the absolute intake value for the specific study depends on the denominator used because food intake data can be presented as per capita intake or for consumers only. To identify the foods mostly consumed, foods are reported and ranked according to total number of times consumed, number of consumers, total intake, or nutrient contribution by individual foods or food groups. Presentation of food intake data primarily depends on a study's aim; reported data thus often are not comparable across studies. Food intake data further depend on the dietary assessment methodology used and foods in the database consulted; and are influenced by the inherent limitations of all dietary assessments. Intake data can be presented as either single foods or as clearly defined food groups. Mixed dishes, reported as such or in terms of ingredients and items added during food preparation remain challenging. Comparable presentation of food consumption data is not always possible; presenting sufficient information will assist valid interpretation and optimal use of the presented data. A checklist was developed to strengthen the reporting of food intake data in science communication.